DESCRIPTION (Adapted from the application) End stage renal disease is associated with several complex nutritional problems. Hypoalbuminemia, the strongest predictor of mortality on dialysis, is related to a combination of nutritional, inflammatory and comorbid factors, but the relative importance of these factors has not been prospectively evaluated. Relative vitamin deficiencies, especially that of B6, B12 and folate, also occur. Hyperhomocysteinemia (hyperHcy), a novel cardio-vascular and thrombotic risk factor, is at least partly correctable with folate and vitamin B6 and B12 supplementation but the clinical benefits of this therapy is not established. The projects outlined in this application will allow Dr. Eustace to continue his mentored research into these two major nutritional problems, hypoalbuminemia and hyperHcy. The PI will: (1A) Conduct a longitudinal analysis of risk factors for dialysis-associated hypoalbuminemia focusing on protein intake and inflammation (C-Reactive Protein), using data collected in the CHOICE cohort study. This is a nationally representative cohort of 925 incident dialysis patients in its 5th year of follow-up, headed by Drs. Powe, Klag and Coresh. (1B) Build on a clinical trial, he recently completed, by conducting a two-center, 2 x 2 factorial trial of 280 recently hospitalized hemodialysis patients, with serum albumins of less then 4.0 g/dl, examining in one arm of the trial the efficacy of oral essential amino acids supplements versus placebo at improving serum albumin levels and reducing hospitalization rates and (1C) Use a decision analysis model to compare the cost-effectiveness, utility and outcomes of oral supplements versus alternative management strategies, including parenteral nutrition, naso-gastric feeding and anabolic agents. (2A) Compare, in the second arm of the above clinical trial, the efficacy of high versus standard dose folate, B6 & B12 supplementation at reducing all cause cardiovascular endpoints and vascular access thromboses. (2B) Perform a meta-analysis of published trials of the benefit of vitamin therapy on actual patient survival. This combination of observational and experimental research under the mentorship of Drs. Coresh and Klag, combined with didactic course work, in the supportive context of the Welch Center will allow Dr. Eustace to build on his current theoretical knowledge, make the transition into an independent clinical scientist and prepare him for a career investigating the role of nutrition in renal disease.